LEUKOCYTE ADHESION IN GASTROINTESTINAL INFLAMMATION

The appropriate recruitment of leukocytes to sites of immune challenge is a fundamental requirement for effective immune defense. Leukocyte trafficking is controlled, to a large extent, by the regulated expression of a variety of cell-surface adhesion receptors. This review provides an introduction to three families of adhesion glycoproteins: the integrins, the immunoglobulin-like adhesion receptors, and the selectins. The roles played by these different adhesion molecules in regulating leukocyte-endothelial cell interactions during the process of neutrophil extravasation is described. The recently characterized beta7 integrin adhesion receptors appear to play an important role in directing lymphocyte homing to the gastrointestinal tract. The importance of cell adhesion molecules in gut immune function is not confined to leukocyte-endothelial adhesion, as shown by a series of recent studies describing adhesion molecule-mediated interactions between leukocytes and intestinal epithelial cell lines. Other studies highlight the importance of leukocyte adhesion in a variety of gastrointestinal inflammatory states including inflammatory bowel disease, nonsteroidal anti-inflammatory drug-induced gastritis, and intestinal ischemia reperfusion injury. The potential for developing new therapeutic agents has provided a major impetus to adhesion molecule research. It is now apparent that many anti-inflammatory drugs, including such familiar agents as corticosteroids and non-steroidal anti-inflammatory drugs, modulate adhesion molecule interactions, and thereby affect the regulation of leukocyte trafficking in intestinal inflammation.